Polygenic risk scores (PRSs) are weighted sums of risk allele counts of single-nucleotide polymorphisms (SNPs) associated with a disease or trait. PRSs are typically constructed based on published results from Genome-Wide Association Studies (GWASs), and the majority of which has been performed in large populations of European ancestry (EA) individuals. Although many genotype-trait associations have generalized across populations, the optimal choice of SNPs and weights for PRSs may differ between populations due to different linkage disequilibrium (LD) and allele frequency patterns. The researcherscompare various approaches for PRS construction, using GWAS results from both large EA studies and a smaller study in Hispanics/Latinos: The Hispanic Community Health Study/Study of Latinos (HCHS/SOL, n=12,803 ). The researchers consider multiple approaches for selecting SNPs and for computing SNP weights.

Human Papillomavirus prevalence among American Indian women of the Great Plains

The Journal of Infectious Diseases, Monday, October 15, 2018

High-risk human papillomavirus (HrHPV) causes cervical cancer. In the U.S., approximately 40% of women aged 14-59 years from all racial and ethnic groups are infected with HPV, and prevalence typically declines with age. However, American Indian women are insufficiently sampled to permit a population-specific estimate of HrHPV prevalence.

Socioeconomic status differences in food consumption following a laboratory-induced stressor

Health Psychology Open, Friday, October 12, 2018

We examined food consumption in response to a laboratory-induced stressor (two challenging neuropsychological tasks) among non-Hispanic White women categorized as lower or higher in socioeconomic status based on education. The two socioeconomic status groups did not differ with respect to current hunger or baseline dietary habits.

Genetic risk scores (GRSs) quantify an individual’s risk for a specified condition using estimates derived from genome-wide association studies. Early studies evaluating the use of cardiovascular disease GRSs comprising known coronary heart disease (CHD) risk variants demonstrate that high GRSs are associated with increased risk for cardiovascular events. However, none of the published CHD GRS studies directly compare the performance of the risk score between men and women.

De novo pathogenic variants in CACNA1E cause developmental and epileptic encephalopathy with contractures, macrocephaly, and dyskinesias

American Journal of Human Genetics, Wednesday, October 10, 2018

Developmental and epileptic encephalopathies (DEEs) are severe neurodevelopmental disorders often beginning in infancy or early childhood that are characterized by intractable seizures, abundant epileptiform activity on EEG, and developmental impairment or regression. CACNA1E is highly expressed in the central nervous system and encodes the α1-subunit of the voltage-gated CaV2.3 channel, which conducts high voltage-activated R-type calcium currents that initiate synaptic transmission.

Optimizing and evaluating biomarker combinations as trial-level general surrogates

Statistics in Medicine, Wednesday, October 10, 2018

We extend the method proposed in a recent work by the Authors for trial-level general surrogate evaluation to allow combinations of biomarkers and provide a procedure for finding the "best" combination of biomarkers based on the absolute prediction error summary of surrogate quality. We use a nonparametric Bayesian model that allows us to select an optimal subset of biomarkers without having to consider a large number of explicit model specifications for that subset.